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    • ENG: Biomedical Engineering: Scholarly Papers
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    •   OpenBU
    • College of Engineering
    • Biomedical Engineering
    • ENG: Biomedical Engineering: Scholarly Papers
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    Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection

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    pgen.1001246.pdf (1.292Mb)
    Date Issued
    2010-12-16
    Related DOI
    10.1371/journal.pgen.1001246
    Author
    Khurana, Jaspreet S.
    Xu, Jia
    Weng, Zhiping
    Theurkauf, William E.
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    Permanent Link
    https://hdl.handle.net/2144/3050
    Citation
    Khurana, Jaspreet S., Jia Xu, Zhiping Weng, William E. Theurkauf. "Distinct Functions for the Drosophila piRNA Pathway in Genome Maintenance and Telomere Protection" PLoS Genetics 6(12):e1001246. (2010)
    Abstract
    Transposons and other selfish DNA elements can be found in all phyla, and mobilization of these elements can compromise genome integrity. The piRNA (PIWI-interacting RNA) pathway silences transposons in the germline, but it is unclear if this pathway has additional functions during development. Here we show that mutations in the Drosophila piRNA pathway genes, armi, aub, ago3, and rhi, lead to extensive fragmentation of the zygotic genome during the cleavage stage of embryonic divisions. Additionally, aub and armi show defects in telomere resolution during meiosis and the cleavage divisions; and mutations in lig-IV, which disrupt non-homologous end joining, suppress these fusions. By contrast, lig-IV mutations enhance chromosome fragmentation. Chromatin immunoprecipitation studies show that aub and armi mutations disrupt telomere binding of HOAP, which is a component of the telomere protection complex, and reduce expression of a subpopulation of 19- to 22-nt telomere-specific piRNAs. Mutations in rhi and ago3, by contrast, do not block HOAP binding or production of these piRNAs. These findings uncover genetically separable functions for the Drosophila piRNA pathway. The aub, armi, rhi, and ago3 genes silence transposons and maintain chromosome integrity during cleavage-stage embryonic divisions. However, the aub and armi genes have an additional function in assembly of the telomere protection complex. Author Summary Transposons and other selfish genetic elements make up a significant fraction of all eukaryotic genomes, and the piRNA pathway appears to have a conserved function in transposon silencing and genome maintenance. However, other functions for this pathway have not been fully explored. Telomeres must be protected from recognition as DNA breaks by the repair machinery, which can covalently ligate unprotected chromosome ends and thus disrupt meiotic and mitotic chromosome segregation. We show that mutations in a subset of piRNA pathway genes disrupt meiotic and mitotic chromosome separation and that these segregation defects are suppressed by a mutation that blocks ligation of non-homologous DNA ends. These mutations also disrupt assembly of the telomere protection complex and reduce expression of a subpopulation of 19- to 22-nt telomere-specific RNA. We therefore propose that a subpopulation of short piRNAs direct assembly of the telomere protection complex.
    Rights
    Khurana et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    • ENG: Biomedical Engineering: Scholarly Papers [107]

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